Four squaraine dyes derived from 2,3,3-trimethylindolenine and 1,1,2-trimethyl-1H-benzo[e]indole with different combinations of barbituric groups attach to the central ring, having ester groups and alkyl chains in the nitrogen atoms of heterocyclic rings were synthesized. These dyes were fully characterized, and their photophysical behavior was studied in ethanol and phosphate-buffered solution. Absorption and emission bands between 631 and 712 nm were detected, with the formation of aggregates in aqueous media, which is typical of this class of dyes. Tests carried out with 1,3diphenylisobenzofuran allowed us to verify the ability of the dyes to produce singlet oxygen. The interaction of synthesized dyes with human serum albumin (HSA) was also evaluated, being demonstrated a linear correlation between fluorescence intensity and protein concentration. The antifungal potential of the dyes against the yeast Saccharomyces cerevisiae was evaluated using a broth microdilution assay. In order to test the photosensitizing capacity of the synthesized dyes, tests were carried out in the dark and with irradiation, using a custom-built light-emitting diode that emits close to the absorption wavelength of the studied dyes. The results showed that the interaction of dyes with HSA and the antifungal activity depends on the different structural modifications of the dyes.

The search for benzo[a]phenoxazines, Nile Blue derivatives, with high antifungal activity and cell labelling capacity based on our previously published works in this type of compounds, led us to the...

Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs. In the recent years, the phenoxazines derivatives, Nile Blue analogues, have been shown to possess anticancer activity, which has created interest in exploring the potential of these compounds as anticancer drugs. In this context, we have synthetized and evaluated the anticancer activity of different benzo[a]phenoxazine derivatives for CRC therapy. Our results revealed that one particular compound, BaP1, displayed promising anticancer activity against CRC cells. We found that BaP1 is selective for CRC cells and reduces cell proliferation, cell survival, and cell migration. We observed that the compound is associated with reactive oxygen species (ROS) generation, accumulates in the lysosomes, and leads to lysosomal membrane permeabilization, cytosolic acidification, and apoptotic cell death. In vivo results using a chicken embryo choriollantoic membrane (CAM) assay showed that BaP1 inhibits tumor growth, angiogenesis, and tumor proliferation. These observations highlight that BaP1 as a very interesting agent to disturb and counteract the important roles of lysosomes in cancer and suggests BaP1 as a promising candidate to be exploited as new anticancer lysosomal-targeted agent, which uses lysosome membrane permeabilization (LMP) as a therapeutic approach in CRC.

Situada no município de Manaus, a Bacia Hidrográfica do Tarumã-Açu (BHTA), nos últimos anos, vem lidando com profundas mudanças no uso e cobertura da terra, principalmente na zona de expansão urbana. Nesse sentido, o objetivo deste artigo é identificar os níveis de suscetibilidade à erosão do solo na BHTA por meio de técnicas de geoprocessamento a partir de variáveis de uso da terra, declividade, tipos de solo e geologia. Para tanto, foram utilizadas imagens do satélite Landsat-8 OLI, o modelo digital de elevação SRTM e dados vetoriais de pedologia e geologia para construção dos mapas temáticos. Com base nesses dados, avaliou-se a suscetibilidade à erosão do solo na bacia, traçando-se a correlação entre as variáveis, possibilitada pelo uso da Linguagem Espacial para Geoprocessamento Algébrico do Spring e da Análise Hierárquica de Processos (AHP). Os resultados apontam, na BHTA, a predominância de relevo ondulado (43,34%) e de Latossolos Amarelos (97,4%) cobertos por florestas; com baixos a moderados níveis de suscetibilidade à erosão do solo. Considerando a rede de drenagem, nota-se a presença de áreas com maiores níveis de suscetibilidade no setor inferior da bacia, enquanto no setor superior esses níveis são menores.

Phenoxazine derivatives such as Nile Blue analogues are assumed to be increasingly relevant in cell biology due to their fluorescence staining capabilities and antifungal and anticancer activities. However, the mechanisms underlying their effects remain poorly elucidated. Using S. cerevisiae as a eukaryotic model, we found that BaP1, a novel 5- and 9-N-substituted benzo[a]phenoxazine synthesized in our laboratory, when used in low concentrations, accumulates and stains the vacuolar membrane and the endoplasmic reticulum. In contrast, at higher concentrations, BaP1 stains lipid droplets and induces a regulated cell death process mediated by vacuolar membrane permeabilization. BaP1 also induced mitochondrial fragmentation and depolarization but did not lead to ROS accumulation, changes in intracellular Ca2+, or loss of plasma membrane integrity. Additionally, our results show that the cell death process is dependent on the vacuolar protease Pep4p and that the vacuole permeabilization results in its translocation from the vacuole to the cytosol. In addition, although nucleic acids are commonly described as targets of benzo[a]phenoxazines, we did not find any alterations at the DNA level. Our observations highlight BaP1 as a promising molecule for pharmacological application, using vacuole membrane permeabilization as a targeted approach.

The demand for new fluorophores for different biological target imaging is increasing. Benzo[a]phenoxazine derivatives are fluorochromophores that show promising optical properties for bioimaging, namely fluorescent emission at the NIR of the visible region, where biological samples have minimal fluorescence emission. In this study, six new benzo[a]phenoxazinium chlorides possessing sulfonamide groups at 5-amino-positions were synthesized and their optical and biological properties were tested. Compared with previous probes evaluated using fluorescence microscopy, using different S. cerevisiae strains, these probes, with sulfonamide groups, stained the vacuole membrane and/or the perinuclear membrane of the endoplasmic reticulum with great specificity, with some fluorochromophores capable of even staining the plasma membrane. Thus, the addition of a sulfonamide group to the benzo[a]phenoxazinium core increases their specificity and attributes for the fluorescent labeling of cell applications and fractions, highlighting them as quite valid alternatives to commercially available dyes.

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